We have been studying the interaction of several ligands with short, DNA triplexes to examine the effect of sequence, cations and base modifications. Several types of triplexes have been examined, such as those with third strands composed of pyrimidines or purines or a mixture of guanine and thymine. While most of the intercalators we have studied can bind to these triplexes, they tend to prefer binding to the duplexes. MidasPlus has proved of great utility in visualizing the types of interactions that can occur with triplexes.